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1.
J Transl Med ; 20(1): 218, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562743

RESUMO

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.


Assuntos
Células Acinares , Endorribonucleases , Animais , Humanos , Camundongos , Células Acinares/metabolismo , Ácido Araquidônico/metabolismo , Proteínas de Transporte/metabolismo , Endorribonucleases/metabolismo , Fibrose , Radioisótopos de Gálio , Camundongos Knockout , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Proteínas Serina-Treonina Quinases , Tripsina/metabolismo , Proteínas Supressoras de Tumor/metabolismo
2.
Cell Physiol Biochem ; 44(3): 1213-1223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29179219

RESUMO

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.


Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim , RNA Longo não Codificante/sangue , Doença Aguda , Área Sob a Curva , Biomarcadores/sangue , Estudos de Coortes , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Curva ROC , Transcriptoma , Transplante Homólogo
3.
Biomed Environ Sci ; 29(3): 197-204, 2016 03.
Artigo em Inglês | MEDLINE | ID: mdl-27109130

RESUMO

OBJECTIVE: To investigate the impact of impoundment and active public health interventions on rodent populations and rodent-borne diseases in the Three Gorges reservoir region from 1997 to 2012. METHODS: Surveillance data from 1997 to 2012 were extracted from the Public Health Surveillance System of The Three Gorges established in 1997. Temporal changes in the incidences of hemorrhagic fever with renal syndrome (HFRS) and leptospirosis, rodent density, pathogen-carrying rates, and their correlations were analyzed. RESULTS: The average indoor and outdoor rodent densities decreased overall from 1997 to 2012. The average densities decreased by 47.72% (from 4.38% to 2.29%) and 39.68% (from 4.41% to 2.66%), respectively, after impoundment (2003-2012) compared with before impoundment (1997-2002). The average annual incidence rates of HFRS and leptospirosis were 0.29/100,000 and 0.52/100,000, respectively, and decreased by 85.74% (from 0.68/100,000 to 0.10/100,000) and 95.73% (from 1.47/100,000 to 0.065/100,000), respectively, after impoundment compared with before impoundment. Incidences of HFRS and leptospirosis appear to be positively correlated with rodent density in the reservoir area. CONCLUSION: This study demonstrated that rodent density and incidences of rodent-borne diseases decreased and were maintained at low levels during construction of the Three Gorges dam. Measures that reduce rodent population densities could be effective in controlling rodent-borne diseases during large-scale hydraulic engineering construction.


Assuntos
Infecções por Hantavirus/veterinária , Leptospirose/virologia , Doenças dos Roedores/epidemiologia , Roedores , Abastecimento de Água , Distribuição Animal , Animais , China/epidemiologia , Reservatórios de Doenças , Infecções por Hantavirus/epidemiologia , Leptospirose/epidemiologia , Densidade Demográfica , Doenças dos Roedores/microbiologia , Doenças dos Roedores/virologia , Estações do Ano , Fatores de Tempo , Zoonoses
4.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(11): 1340-1344, 2016 Nov.
Artigo em Zh | MEDLINE | ID: mdl-30641628

RESUMO

Objective To observe the effect of Fuzheng Kang'ai Recipe (FKR) combined ge- fitinib on the proliferation and apoptosis of lung cancer A549 cells , and to study its potential synergistic mechanish with gefitinib. Methods The effects of FKR (0. 211, 0. 316, 0. 474, 0. 711, 1. 067, 1. 600, 2. 400, 3. 600 mg/mL) combined gefitinib (3. 95, 5. 92, 8. 18, 13. 33, 20. 00, 30. 00, 45. 00, 67. 50 µmol/ L) on the proliferation of A549 cells were detected by MTT assay. The apoptosis of A549 cells in the control group (complete culture medium) , FKR (1. 6 mg/mL) , gefitinib (45 µmol/L) , and FKR plus gefitinib (1. 6 mg/mL +45 µmol/L) were detected by flow cytometry (FCM). Their expressions of epidermal growth factor receptor (EGFR) , phosphorylating epidermal growth factor receptor ( p-EGFR) , enhancer of zeste homolog 2 (EZH2), peroxisome proliferator-activated receptor-γ ( PPAR-γ) , and P53 protein in A549 cells were detected by Western blot. Results Both FKR and gefitinib could inhibit the proliferation of A549 cells. The apoptotic rate was 12. 6% ±4. 5% in the FKR combined gefitinib group, obviously higher than that of the FKR group (4. 6% ± 0. 7%) and the gefitinib group (7. 8% ± 2. 7%) , showing statistical difference (P <0. 05). Compared with the control group, the expressions of p-EGFR and EZH2 were sig- nificantly down-regulated (P <0. 05) , the expressions of PPAR-γ and P53 protein were up-regulated in the FKR combined gefitinib group (P <0. 05); the expression of EZH2 was down-regulated in the gefitinib group and the FKR group (P <0. 05) ; the expression of PPAR-y was up-regulated in the FKR group (P < 0. 05). Compared with the gefitinib group, the expression of p-EGFR was down-regulated, and the expression of PPAR-γ was up-regulated in the FKR combined gefitinib group (both P <0. 05). Compared with the FKR group, the expression of p-EGFR was down-regulated in the FKR combined gefitinib group (P < 0. 05). Conclusions Combination of FKR and gefitinib could significantly inhibit the proliferation and growth of A549 cells,and induce cell apoptosis. Its potential synergistic mechanism of anti-tumor activities might be associated with down-regulating mRNA expressions of p-EGFR and EZH2, and up-regulating protein expressions of PPAR-y and P53.


Assuntos
Antineoplásicos , Apoptose , Carcinoma Pulmonar de Células não Pequenas , Medicamentos de Ervas Chinesas , Gefitinibe , Neoplasias Pulmonares , Células A549 , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Medicamentos de Ervas Chinesas/uso terapêutico , Receptores ErbB , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas
5.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(2): 160-5, 2016 Feb.
Artigo em Zh | MEDLINE | ID: mdl-27078990

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of Jianpi Liqi Yiliu Formula (JLYF) combined with cytokine-induced killer (CIK) cells for treating patients with advanced hepatocellular carcinoma (HCC). METHODS: Between January 2011 and January 2014, 60 advanced HCC patients were enrolled in this study, who were assigned to the treatment group and the control group according to their willingness for taking JLYF, 30 cases in each group. All patients received CIK cell treatment: 1 x 109-3 x 109 each time, by intravenous dripping from the 1st day to the 3rd day, once per day. Besides, patients in the treatment group took JLYF decoction, while those in the control group took Chinese medical decoction by syndrome typing. All patients received treatment of at least two cycles. The time to progression (TTP) , overall survival (OS), disease control rate (DCR), performance status scale (PS), Child-Pugh scale, and adverse reactions were observed, and subgroup analyzed. RESULTS: To May 31, 2014, all patients reached the clinical endpoint. TTP was 3.5 months (95% Cl: 3.30-4.10) in the treatment group, better than that (2.5 months, 95% CI: 2.32-2.68) of the control group (P < 0.05). DCR was 36.7% in the treatment group and 30.0% in the control group (P > 0.05). OS was 5.2 months (95% CI: 4.53-5.87) in the treatment group and 4.6 months (95% CI: 4.06-5.14) in the control group (P > 0.05). The PS scale was 1.60 ± 0.10 after treatment, lower than that (1.80 ± 0.09) before treatment in the treatment group (P < 0.05). When the PS scale was 0-2 or Child-Pugh scale was class A, TTP was longer in the treatment group than in the control group (P < 0.05). No adverse reaction occurred in the two groups during the treatment course. CONCLUSIONS: The combination of JLYF with ClK cell treatment could prolong advanced HCC patients' TTP, improve PS scale, as compared with syndrome typed Chinese medical decoction treatment group. Besides, when the PS scale was 0-2 or Child-Pugh scale was class A, it was a better treatment program for advanced HCC patients.


Assuntos
Carcinoma Hepatocelular/terapia , Células Matadoras Induzidas por Citocinas/citologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas/terapia , Terapia Baseada em Transplante de Células e Tecidos , Progressão da Doença , Humanos
6.
Tumour Biol ; 36(10): 8159-66, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25990459

RESUMO

Bladder cancer ranks the second most common genitourinary tract cancer, and muscle-invasive bladder cancer (MIBC) accounts for approximately 25 % of all bladder cancer cases with high mortality. In the current study, with a total of 202 treatment-naïve primary MIBC patients identified from The Cancer Genome Atlas dataset, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in MIBC, with the aim to investigate the relationship of miRNA expression with the progression and prognosis of MIBC, and generate a miRNA signature of prognostic capabilities. In the progression-related miRNA profiles, a total of 47, 16, 3, and 84 miRNAs were selected for pathologic T, N, M, and histologic grade, respectively. Of the eight most important progression-related miRNAs, four (let-7c, mir-125b-1, mir-193a, and mir-99a) were significantly associated with survival of patients with MIBC. Finally, a four-miRNA signature was generated and proven as a promising prognostic parameter. In summary, this study identified the specific miRNAs associated with the progression and aggressiveness of MIBC and a four-miRNA signature as a promising prognostic parameter of MIBC.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Musculares/genética , Neoplasias Musculares/mortalidade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Carcinoma Papilar/genética , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia
7.
Biosci Biotechnol Biochem ; 79(8): 1266-71, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26024368

RESUMO

To optimize Agrobacterium-mediated transient transformation assay in mulberry (Morus alba L.), various infiltration methods, Agrobacterium tumefaciens (A. tumefaciens) strains, and bacterial concentrations were tested in mulberry seedlings. Compared with LBA4404, GV3101 harboring pBE2133 plasmids presented stronger GUS signals at 3 days post infiltration using syringe. Recombinant plasmids pBE2133:GFP and pBE2133:GFP:MaFT were successfully constructed. Transient expression of MaFT:GFP protein was found in leaves, petiole (cross section), and shoot apical meristem (SAM) of mulberry according to the GFP signal. Moreover, MaFT:GFP mRNA was also detected in leaves and SAM via RT-PCR and qRT-PCR. An efficient transient transformation system could be achieved in mulberry seedlings by syringe using A. tumefaciens GV3101 at the OD600 of 0.5. The movement of MaFT expression from leaves to SAM might trigger the precocious flowering of mulberry.


Assuntos
Proteínas de Arabidopsis/genética , Morus/genética , Folhas de Planta/genética , Plantas Geneticamente Modificadas/genética , Agrobacterium tumefaciens/genética , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Frutas/genética , Regulação da Expressão Gênica de Plantas , Morus/crescimento & desenvolvimento , Folhas de Planta/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plasmídeos , Plântula/genética
8.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(2): 162-6, 2014 Feb.
Artigo em Zh | MEDLINE | ID: mdl-24672939

RESUMO

OBJECTIVE: To evaluate the prognostic factors in treating primary liver cancer (PLC) patients by Pi-strengthening and qi-regulating method (PSQRM), thus providing evidence and optimizing Pi-strengthening and qi-regulating program. METHODS: Clinical data of 151 PLC patients treated by PSQRM at Oncology Department, Guangdong Provincial Hospital of Traditional Chinese Medicine from May 2007 to March 2009 were retrospectively analyzed. The univariate analysis was determined to analyze possible prognostic factors. Selected key factors were introduced into the COX proportional hazard model, and multivariate analysis was carried out. RESULTS: The 1-year survival rate was 21.85%, the median survival time was 6.80 months, and the mean survival time was 8.98 months. The univariate analysis showed that Chinese medicine (CM) syndrome types, clinical symptoms at the initial diagnosis, ascites, tumor types, ratios of foci, portal vein tumor thrombus, intrahepatic metastasis, a-fetoprotein (AFP) levels, total bilirubin classification, albumin classification, Child-Pugh classification, and domestic staging of liver cancer were significant prognostic factors (P < 0.05). The statistic data of multivariate analysis indicated that CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer were independent factors influencing prognosis (P < 0.05). CONCLUSION: The prognosis of PLC treated with PSQRM is determined by multiple factors including CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Medicina Tradicional Chinesa/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(7): 911-4, 2013 Jul.
Artigo em Zh | MEDLINE | ID: mdl-24063211

RESUMO

OBJECTIVE: To explore the distribution of Chinese medicine (CM) syndrome types in primary liver cancer (PLC) and their differences of the survival time. METHODS: From May 2007 to March 2009, recruited were 151 PLC inpatients at Department of Tumor, Guangdong Provincial Hospital of Traditional Chinese Medicine. Their survival time were statistically calculated. Patients' average survival time and median survival time were calculated using Kaplan-Meier method. The Log-rank test was used to analyze their differences of survival time among different CM syndrome types. RESULTS: The proportion of CM syndrome types in PLC patients were ranked from high to low as follows: mutual accumulation of dampness and blood stasis syndrome [MADBSS, 43.0% (65/151)], Gan-stagnation Pi-deficiency syndrome [GSPDS, 34.4% (52/151)], qi stagnation blood stasis syndrome [QSBSS, 9.3% (14/151)], retention of damp-heat syndrome [RDHS, 8.6%(13/151)], and Gan-Shen yin deficiency syndrome [GSYDS, 4.6% (7/ 151)]. The median survival time of different CM syndrome types were ranked from longer to shorter as follows: GSPDS (14.77 months), QSBSS (6.13 months), RDHS (5.27 months), MADBSS (4.78 months), and GSYDS (0.80 months). The mean survival times were ranked from longer to shorter as follows: GSPDS (12.40 months), QSBSS (8.84 months), MADBSS (6.99 months), RDHS (7.08 months), and GSYDS (0.72 months). There was statistical difference in the difference of the survival time among different CM syndrome types (P < 0.05). CONCLUSIONS: GSPDS and MADBSS were the most common CM syndrome types in PLC patients. There was difference in the survival time between GSPDS and MADBSS/between RDHS and GSYDS. There was difference in the survival time between MADBSS and GSYDS. Patients of GSPDS might get the best prognosis, while patients of GSYDS might get the poorest prognosis.


Assuntos
Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Medicina Tradicional Chinesa , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Deficiência da Energia Yang , Deficiência da Energia Yin
10.
Front Pharmacol ; 14: 1331371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259285

RESUMO

Objectives: Accumulating evidence are available on the efficacy of high-dose isoniazid (INH) for multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to perform a systematic review and meta-analysis to compare clinical efficacy and safety outcomes of high-dose INH- containing therapy against other regimes. Methods: We searched the following databases PubMed, Embase, Scopus, Web of Science, CINAHL, the Cochrane Library, and ClinicalTrials.gov. We considered and included any studies comparing treatment success, treatment unsuccess, or adverse events in patients with MDR-TB treated with high-dose INH (>300 mg/day or >5 mg/kg/day). Results: Of a total of 3,749 citations screened, 19 studies were included, accounting for 5,103 subjects, the risk of bias was low in all studies. The pooled treatment success, death, and adverse events of high-dose INH-containing therapy was 76.5% (95% CI: 70.9%-81.8%; I2: 92.03%), 7.1% (95% CI: 5.3%-9.1%; I2: 73.75%), and 61.1% (95% CI: 43.0%-77.8%; I2: 98.23%), respectively. The high-dose INH administration is associated with significantly higher treatment success (RR: 1.13, 95% CI: 1.04-1.22; p < 0.01) and a lower risk of death (RR: 0.45, 95% CI: 0.32-0.63; p < 0.01). However, in terms of other outcomes (such as adverse events, and culture conversion rate), no difference was observed between high-dose INH and other treatment options (all p > 0.05). In addition, no publication bias was observed. Conclusion: In MDR-TB patients, high-dose INH administration is associated with a favorable outcome and acceptable adverse-event profile. Systematic review registration: identifier CRD42023438080.

11.
Food Res Int ; 157: 111369, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761634

RESUMO

The medium-chain fatty acid ethyl esters (MCFAEEs) are a group of important aroma compounds generated during wine production. Wine alcohol fermentation involves several redox processes, which are affected by the oxidation-reduction potential (ORP). However, the mechanism via which ORP regulates MCFAEE production remains unclear. To investigate the effect of ORP on MCFAEE production, wine alcohol fermentation was performed using Saccharomyces cerevisiae under different ORPs. The results demonstrated that the ORPs studied (except for 90 mV) did not significantly affect cell growth, sugar consumption, and ethanol production, while the MCFAEE concentration in the simulated wines can be manipulated by ORP operation. MCFAEE levels increased till 96 h, and then decreased. The maximum MCFAEE level of 1222.97 µg/L was obtained after 96 h at 0 mV, which was 45.32% higher than that of the control. During the increase, higher relative expression of ACC1, FAS1, FAA2 and EEB1, elevated external citric acid flux, and moderate intracellular NADP+/NADPH ratio were observed at 0 mV compared to that at other ORPs. During the decrease, lowest relative expression of POX1 was detected at 0 mV. We showed for the first time the relationship between ORP operation and MCFAEE production in winemaking, which will improve the aroma quality of wine.


Assuntos
Vinho , Ésteres/análise , Ácidos Graxos/metabolismo , Fermentação , Oxirredução , Saccharomyces cerevisiae/metabolismo , Vinho/análise
12.
Cell Death Dis ; 13(10): 893, 2022 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273194

RESUMO

Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1Tg) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.


Assuntos
Adenosina Trifosfatases , Lisofosfatidilcolinas , Macrófagos , Pancreatite Crônica , Animais , Camundongos , Células Acinares/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Ceruletídeo/toxicidade , Histonas/metabolismo , Inflamação/metabolismo , Lisofosfatidilcolinas/genética , Lisofosfatidilcolinas/metabolismo , Macrófagos/metabolismo , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/genética , Pancreatite Crônica/metabolismo , Proteínas de Transferência de Fosfolipídeos/genética , Proteínas de Transferência de Fosfolipídeos/metabolismo , Fatores de Transcrição/metabolismo
13.
Lancet Infect Dis ; 21(5): 617-628, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33476567

RESUMO

BACKGROUND: Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan. METHODS: This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect. FINDINGS: 27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2-16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0-1 years were significantly more likely to be infected than children aged 2-5 years (odds ratio [OR] 2·20, 95% CI 1·40-3·44) and children aged 6-12 years (1·53, 1·01-2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28-1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14-0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30-1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 [95% CI 0·24-0·26] to 0·12 [0·10-0·13]) and by 63% among secondary cases (from 0·17 [0·16-0·18] to 0·063 [0·057-0·070]). INTERPRETATION: Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available. FUNDING: National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.


Assuntos
COVID-19/transmissão , SARS-CoV-2 , Adolescente , Adulto , Fatores Etários , Idoso , COVID-19/etiologia , Criança , Pré-Escolar , China/epidemiologia , Suscetibilidade a Doenças , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
14.
J Environ Sci Health B ; 45(2): 152-61, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20390945

RESUMO

An efficient and sensitive method for simultaneous determination of 38 pesticides in agricultural drainage waters and soils has been developed and validated. Water samples were extracted using solid-phase extraction with C18 cartridges while solid samples (suspended particle matter and soil) were extracted by using the quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction method. The target pesticides were analyzed by using gas chromatography-mass spectrometry with electron impact ionization. The proposed method allowed a simultaneous determination and confirmation of a large number of pesticides in agricultural drainage waters, suspended particle matters and soils/sediments with a good reproducibility and low detection limits. The developed method was applied to a survey of pesticides in a vegetable growing area of Guangzhou, China. The pesticides commonly found in the area were butachlor, carbofuran, dichlorvos, fipronil, isocarbophos and pyridaben.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Herbicidas/análise , Inseticidas/análise , Resíduos de Praguicidas/análise , Solo/análise , Água/química , Agricultura , Limite de Detecção , Reprodutibilidade dos Testes , Poluentes do Solo/análise , Extração em Fase Sólida , Poluentes Químicos da Água/análise
15.
Zhonghua Yu Fang Yi Xue Za Zhi ; 44(5): 438-43, 2010 May.
Artigo em Zh | MEDLINE | ID: mdl-20654235

RESUMO

OBJECTIVE: To sequence and analyze the complete genome of two new Japanese encephalitis virus (JEV) strains isolated from mosquitoes collected in Hubei province in 2008, and to understand the molecular biological characteristics of JEV in this area. METHODS: RT-PCR was used to amplify the fragments of HBZG08-09 strain and HBZG08-55 strain with 16 pairs overlapping primers after they had been recovered and identified, then the full-length genome was obtained by sequencing and splicing. Biological sequence alignment, nucleotide and amino acid sequence analysis, phylogenetic analysis and analysis of amino acid differences were performed by the software of Clustal X (1.83), MegAlign, Mega (4.0) and Genedoc (3.2). RESULTS: The genome of two new strains were both 10 965 nucleotides in length with a single open reading frame from 96 to 10 392 coding for a 3432 amino acid poly-protein, the homology of nucleotide and amino acid sequence between two isolates were 98.2% and 99.7% respectively. Further study showed that the new strains were both belonging to genotype I. Two new strains were most closely related to isolates obtained from Henan and Zhejiang province in recent years. Compared with the live attenuated vaccine strain SA-14-14-2 in China, HBZG08-09 strain had 82 amino acid divergence; HBZG08-55 had 84 amino acid divergences. But the amino acid difference occurred in sites were not the key ones affecting the toxicity or antigenic of JEV. CONCLUSION: Two new JEV isolates were both belonging to genotype I, and the key sites of amino acid were not changed.


Assuntos
Culicidae/virologia , Vírus da Encefalite Japonesa (Espécie)/genética , Genoma Viral , Animais , China , Vírus da Encefalite Japonesa (Espécie)/classificação , Vírus da Encefalite Japonesa (Espécie)/isolamento & purificação , Genótipo , Dados de Sequência Molecular , Filogenia , RNA Viral , Alinhamento de Sequência
16.
Zhongguo Zhen Jiu ; 40(1): 37-40, 2020 Jan 12.
Artigo em Zh | MEDLINE | ID: mdl-31930897

RESUMO

OBJECTIVE: To observe the effect of hypnosis on pain and fear in the healthy acupuncture subjects. METHODS: A total of 52 healthy subjects were randomized into an observation group and a control group, 26 cases in each one. In the observation group, the subjects received the first-time acupuncture under hypnosis. After wakened up and 30 min later, the subjects received the second-time acupuncture under clear consciousness condition. In the control group, the subjects received the first-time acupuncture under clear consciousness condition, 30 min later, received the second-time acupuncture under hypnosis. Likert scale was adopted to investigate the relaxation, pain sensation and the willingness in the subjects at the normal condition before acupuncture, after the first-time and the second-time acupuncture of the two groups separately. Using Boeran electronic blood pressure monitor, the pulse and blood pressure were measured in the subjects at the normal condition and after the first-time acupuncture of the two groups. RESULTS: Compared with the normal condition, the relaxation degree was increased, the pain sensation decreased and the willingness enhanced after acupuncture either after hypnosis or after wakened-up in the observation group (P<0.001). The difference was not significant in each index between acupuncture after hypnosis and acupuncture after wakened-up in the observation group (P>0.05). In the control group, compared with the normal condition, after the first-time acupuncture (acupuncture in clear consciousness), the relaxation degree was decreased, pain was alleviated and the willingness was increased when acupuncture was exerted once again (P<0.001, P<0.05); compared with the normal condition, after the second-time acupuncture (acupuncture after hypnosis), pain was alleviated and the willingness increased (P<0.001), but the difference in relaxation was not significant (P>0.05); compared with the first-time acupuncture, the relaxation degree was increased, pain alleviated and willingness enhanced after the second-time acupuncture (acupuncture after hypnosis) (P<0.05, P<0.001). Compared with the control group after the first-time acupuncture (acupuncture in clear consciousness), the relaxation degree and willingness were increased and the pain sensation was reduced in the observation group during acupuncture either after hypnosis or after wakened-up (P<0.001). Compared with the control group the second-time acupuncture (during acupuncture after hypnosis), the relaxation degree was increased and pain sensation reduced in the observation group during acupuncture either after hypnosis or after wakened-up (P<0.01, P<0.001), but the difference was not significant in willingness (P>0.05). In the control group, compared with the normal condition, the pulse was faster, both the diastolic pressure and systolic pressure were increased after the first-time acupuncture (P<0.05, P<0.01). In the observation group, compared with the normal condition, the pulse was getting slow and blood pressure was reduced after the first-time (acupuncture under hypnosis, P<0.01). Compared with the first-time acupuncture in the control group, pulse was getting slow and blood pressure was reduced in the observation group after acupuncture under hypnosis (P<0.001). CONCLUSION: During acupuncture, with hypnosis combined, the fear alleviates, pain reduces and the willingness of acupuncture increases in the subjects.


Assuntos
Terapia por Acupuntura , Medo , Hipnose , Manejo da Dor , Humanos , Dor
17.
Nat Microbiol ; 5(5): 675-678, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32265517

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei Province, China in late December 2019. We re-analysed 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020 and found that 9 of the 640 throat swabs were positive for SARS-CoV-2 RNA by quantitative PCR, suggesting community transmission of SARS-CoV2 in Wuhan in early January 2020.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Criança , Pré-Escolar , China , Infecções por Coronavirus/virologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Adulto Jovem
18.
Theranostics ; 10(18): 8298-8314, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724472

RESUMO

Background: There is no curative therapy for severe acute pancreatitis (SAP) due to poor understanding of its molecular mechanisms. Endoplasmic reticulum (ER) stress is involved in SAP and increased expression of ATF6 has been detected in SAP patients. Here, we aimed to investigate the role of ATF6 in a preclinical SAP mouse model and characterize its regulatory mechanism. Methods: Pancreatic tissues of healthy and SAP patients were collected during surgery. Humanized PRSS1 transgenic mice were treated with caerulein to mimic the SAP development, which was crossed to an ATF6 knockout mouse line, and pancreatic tissues from the resulting pups were screened by proteomics. Adenovirus-mediated delivery to the pancreas of SAP mice was used for shRNA-based knockdown or overexpression. The potential functions and mechanisms of ATF6 were clarified by immunofluorescence, immunoelectron microscopy, Western blotting, qRT-PCR, ChIP-qPCR and luciferase reporter assay. Results: Increased expression of ATF6 was associated with elevated apoptosis, ER and mitochondrial disorder in pancreatic tissues from SAP patients and PRSS1 mice. Knockout of ATF6 in SAP mice attenuated acinar injury, apoptosis and ER disorder. AIFM2, known as a p53 target gene, was identified as a downstream regulatory partner of ATF6, whose expression was increased in SAP. Functionally, AIFM2 could reestablish the pathological disorder in SAP tissues in the absence of ATF6. p53 expression was also increased in SAP mice, which was downregulated by ATF6 knockout. p53 knockout significantly suppressed acinar apoptosis and injury in SAP model. Mechanistically, ATF6 promoted AIFM2 transcription by binding to p53 and AIFM2 promoters. Conclusion: These results reveal that ATF6/p53/AIFM2 pathway plays a critical role in acinar apoptosis during SAP progression, highlighting novel therapeutic target molecules for SAP.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Mitocondriais/genética , Pâncreas/patologia , Pancreatite/genética , Proteína Supressora de Tumor p53/genética , Células Acinares/patologia , Fator 6 Ativador da Transcrição/genética , Adulto , Animais , Apoptose/genética , Estudos de Casos e Controles , Ceruletídeo/administração & dosagem , Ceruletídeo/toxicidade , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Pâncreas/citologia , Pancreatite/induzido quimicamente , Pancreatite/patologia , Ativação Transcricional , Tripsina/genética
19.
Sci Total Environ ; 407(2): 962-74, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19004474

RESUMO

An analytical method for phenolic endocrine disrupting chemicals and acidic pharmaceuticals in river water was developed using gas chromatography mass spectrometry (GC-MS) coupled with negative chemical ionization (NCI) technique, and used for the determination of these compounds in the Pearl Rivers (Liuxi, Zhujiang and Shijing Rivers). Derivatization using pentafluorobenzoyl chloride (PFBOCl) and pentafluorobenzyl bromide (PFBBr) before GC-MS analysis were applied and optimized for phenolic compounds and acidic compounds, respectively. The target compounds were analyzed for river waters from the upstream to downstream of the Pearl Rivers. Phenolic compounds 4-tert-octylphenol (4-t-OP), 4-nonylphenol (4-NP), bisphenol-A (BPA), estrone (E1), estradiol (E2) and triclosan (TCS) were detected at trace or low levels in the water samples from Liuxi River and Zhujiang River. Diethylstilbestrol (DES) was not detected in the Pearl Rivers. The highest concentrations of the phenolic compounds were found in Shijing River, and they were 3150 ng/L for 4-t-OP, 11,300 ng/L for 4-NP, 1040 ng/L for BPA, 79 ng/L for E1, 7.7 ng/L for E2 and 355 ng/L for TCS, respectively. Only a few acidic pharmaceuticals were detected at low concentrations in water from Liuxi River and Zhujiang River, but the highest concentrations for the acidic pharmaceuticals were also found in Shijing River. The highest concentrations detected for clofibric acid, ibuprofen, gemfibrozil, naproxen, mefenamic acid and diclofenac were 17 ng/L, 685 ng/L, 19.8 ng/L, 125 ng/L, 24.6 ng/l and 150 ng/L, respectively. The results suggest Liuxi and Zhujiang Rivers are only slightly contaminated and can be used as drinking water sources, but Shijing River is heavily polluted by the wastewater from nearby towns.


Assuntos
Ácidos Carboxílicos/análise , Disruptores Endócrinos/análise , Cromatografia Gasosa-Espectrometria de Massas , Preparações Farmacêuticas/análise , Fenóis/análise , Rios/química , Poluentes Químicos da Água/análise , Ácidos Carboxílicos/farmacologia , China , Geografia , Preparações Farmacêuticas/química , Fenóis/farmacologia
20.
J Colloid Interface Sci ; 542: 177-186, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30738310

RESUMO

A novel composite vanadium-blocking proton exchange membrane for vanadium redox flow battery (VRB) was designed and constructed by immobilizing phosphotungstic acid (PWA) on Nano Kevlar Fibers (NKFs) via a solution-casting method. The proton/vanadium selectivity of the composite membrane is greatly improved by incorporating the complex formed by NKFs and PWA into the Nafion matrix. Simple tuning of the complex doping quantity results in different composite membranes with superior vanadium barrier properties (namely, a minimum vanadium permeability of 2.46 × 10-7 cm2 min-1). This coupled with proton conductivities reaching 0.061 S cm-1 at room temperature indicates a proton/vanadium selectivity of 2.48 × 105 S min cm-3, which is 6.3 times higher than that of recast Nafion (0.34 × 105 S min cm-3). When tested in a VRB, the performance of the single cell assembled with the composite membrane greatly outperforms that with recast Nafion at current densities ranging from 40 to 100 mA cm-2.

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